Effects of Humid Air Breathing during Arm or Treadmill Exercise on Exercise-induced Bronchoconstriction and Refractoriness 1- 3

BRIAN A. WILSON, ODED BAR-OR, and LAURA G. SEED

Introduction

Bronchoconstriction can result from a variety of stimuli in asthmatics. These include chemical stimuli such as histamine and methacholine (1), allergens (2), hyperventilation (3), cold air exposure (4), and exercise (5). Bronchial responsiveness is often reduced if repeated challenges are given. In exercise-induced bronchoconstriction (EIB), for example, most subjects will respond with a reduced bronchoconstriction after a second exercise bout, up to 4 h after the initial bout, and this time period is referred to as the refractory period (6). Likewise, a second challenge with histamine results in a smaller degree of bronchoconstriction than that after the initial challenge. This tachyphylaxis to inhaled histamine, as well as the exercise refractoriness, can be prevented by pretreatment with indomethacin (7, 8). It has also been shown that some protection from EIB after exercise in cold, dry air can be achieved by prior exercise that does not produce EIB (9). In addition, because only protection to subsequent exercise with the same muscle group has been demonstrated, it is possible that some "exercise factor" released from active skeletal muscle is involved in the refractory response. The severity of the initial EIB response can be modulated by several factors, including drug treatment (10), alteration of environmental conditions (11), and use of different exercise modes (12). It is at present unclear whether exercise, airway cooling, and drying, or bronchoconstriction itself are required to induce exercise refractoriness. The purpose of this study, therefore, was to examine the effectiveness of prior treadmill and arm-cranking exercise, in both dry and humid thermoneutral environments, in producing refractoriness to a standard treadmill challenge.

SUMMARY Although it has been reported that inhibitory prostaglandins may be a causal factor in exercise refractoriness, it is still unclear whether exercise-Induced bronchoconstrlction (EIB) and/or other specific "exercise factors" are necessary to trigger their release and render a subject refractory to subsequent exercise. The purpose of this study was to determine whether non-EtB-producing exercise with the legs or arms could produce refractoriness to a standard treadmill challenge. Eight asthmatic subjects with EIB completed three sessions consisting of two exercise challenges separated by a 30-mln rest. In all seSSions, the second challenge was done on a treadmill while breathing dry air. Conditions for Challenge 1 were the following: Session A = treadmill, dry air; Session B = treadmill, humid air; Session C = arm cranking, humid air. All three conditions produced a significant degree of refractoriness. There was a tendency for the percent protection index to be greater for Session A; however, no significant differences were found among the three sessions. Therefore, it can be concluded that although both exercise and bronchoconstrlctlon may playa role in producing the refractory period, neither severe bronchoconstriction nor intense exercise with the same muscle groups are required to produce refractoriness. AM REV RESPIR DIS 1990; 142:349-352

Methods Subjects 1\velve asthmatic subjects originally volunteered for the study. Of these 12, eight met the criteria of having EIB and showing a refractory period. These eight (five men and three women, 19 to 29 yr of age) (table I) volunteered to participate, after having given informed consent. All were known to have recurrent, reversible, airway obstruction not necessarily due to exercise. At the time of this study, the subjects were not taking any type of medication on a daily basis but they did use salbutamol to relieve the asthma when it did occur.

Design and Protocols All subjects attended three sessions, each consisting of two exercise challenges (CH-I and CH-2) separated by a 30-min rest. All sessions were conducted on each subject at the same time of day in order to reduce the effect of diurnal variation. Sessions were at least two days apart and testing on anyone individual was completed within 2 wk. CH-I of each session varied in mode of exercise and inspired air conditions. The inspired air conditions were (1) dry air "standard bout" (250/0 relative humidity or less; Session A), which was supplied to the subjects from a compressed medical air tank, and (2) humid air (85 % relative humidity or more; Sessions B and C), which was supplied to the

subject from a compressed medical air tank after having passed through heated water and a Tissot gasometer (Warren E. Collin, Braintree, MA). The inspired air conditions for CH-2 of all sessions was dry air (25% relative humidity or less). For each exercise challenge, the subject breathed the test air for 5 min before exercise, during exercise, and 5 min after exercise. The mode of exercise was treadmill running for all sessions except CH-I of Session C, which was arm cranking. All treadmill challenges were of the same intensity for each subject, 85 to 90% of their predicted maximal heart rate (HR), and were 6 min in duration. The exercise intensities for seated arm cranking were set near the maximal intensity the subjects could maintain for 6 min. FVC maneuvers were performed before breathing the test air, while breathing the test (Received in original form May 19, 1989 and in revised form February 28, 1990) I From the School of Human Biology, University of Guelph, Guelph, and the Childrens Exercise and Nutrition Centre, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. 2 Supported in part by a grant from the Banting Foundation. 3 Correspondence and requests for reprints should be addressed to Dr. Brian A. Wilson, School of Human Biology, University of Guelph, Guelph, ON, Canada NIG 2Wl.

349

350

WILSON, BAR-OR, AND SEED

TABLE 1

differences in pre-exercise pulmonary function, exercise RHL, and postexercise decreases in FEV, and MEF.o • A repeated measures ANOVA was employed to identify any differences in percent protection index across conditions. All tests used a confidence level of p < 0.05.

SUBJECT CHARACTERISTICS

(yr)

Height (cm)

Weight

Sex

(kg)

FEV,

MEF.o

M M F F M F M M

22 20 19 20 29 19 23 21

180 171 169 162 183 172 188 183

79.0 82.6 71.6 53.0 75.1 65.9 82.6 83.6

92 95 80 100 105 88 82 92

94 82 85 102 95 94 84 98

Age Subject CB OM HH NL MF CP BW SS

Baseline Resting (% predicted)

air just before the exercise challenge (preexercise), and after the exercise challenge at zero, 2, 4, 6, 10, and 15 min. The pre-exercise value was compared to the values obtained before any testing to confirm that the subjects were not starting the exercise already bronchoconstricted. The pre-exercise value before each trial for each subject was always within 6070 of the resting value. Temperatures of expired and inspired air were monitored for the full 6 min. The expired air was collected during the last minute of exercise, and the oxygen and carbon dioxide content was analyzed to calculate oxygen consumption (Vo,) and carbon dioxide production (Veo,).

Apparatus The volume of inspired air was measured by a Parkinson Cowan dry gas volumeter (Bionetics, Toronto, Ontario, Canada). The subject breathed the inspired air through a Daniels'valve; the air came through the volumeter directly from a compressed medical air tank or indirectly via a Tissot gasometer. Temperature of the expired air was measured using a YSI #421 thermistor (Yellow Springs Instrument Co., Inc., Yellow Springs, OH) with a time constant of 0.3 s. The thermistor was located in the Daniels' valve 2 cm from the mouth. The concentration of expired oxygen and carbon dioxide was measured using af S-3A oxygen analyzer (AMETEK, Pittsburgh, PAl and a Gould-Godart capnograph (MK II; Roxon Medi-tech, Montreal, Quebec, Canada), which were calibrated using gas tanks previously analyzed by the micro-Scholander technique. Maximal expiratory flow (MEF 50) and FEV1 were measured simultaneously from a FVC maneuver using a Fleisch pneumotachograph (size no. 3; Gould Med. Products, Bilthoven, Netherlands) and a Hewlett-Packard digital analyzer (Model 47303A; HewlettPackard, Waltham, MA). The maximal expiratory flow-volume (MEFV) curve was recorded on a Honeywell X.:y recorder (Model XY530; Esterline Angus, Indianapolis, IN). A Warren E. Collins treadmill was used for running, (Warren E. Collins, Braintree, MA) and an electronically braked Quinton cycle ergometer (Model QI844; Quinton Instruments,

Results

Values for all circulatory, ventilatory, and metabolic variables, as measured in the last minute of exercise, are listed in table 2. When all treadmill challenges were compared to the standard test, there was no significant difference in HR, minute ventilation (VE), respiratory frequency (f), tidal volume (VT), and Veo,. The VOl for Session B CH-l was significantly higher than the standard bout, whereas VE/VO, of that challenge test was significantly lower. When the arm-cranking challenge values were compared to the standard test, HR, VE, Veo" and VOl were significantly lower, with VE/VO, being significantly higher. The RHL obtained for each challenge depended, as expected, on the conditions of inspired air. RHL was not different among any of the dry air tests, averaging 1.35 kcal/min, whereas the humid treadmill and arm-cranking tests were significantly lower with means of 1.00 and 0.80 kcalimin, respectively. There were no significant differences between pre-exercise values for MEF 50 or FEVl for CH-I across all trials. The individual subject data for FEV" preexercise and postexercise, and percent protection index are presented in table 3. The mean response for FEV! and MEF 50 after each challenge are shown in figure 1. The standard bout resulted in a decrease of 42.8% for MEF50 and 30.9070 for FEV,. This decrease was greater in the standard bout than in any of the other challenges. The lower decrease after CH-2 of each session indicates a significant refractory period in each case.

Seattle, WA) was positioned in such a manner that the arm-work challenge could be performed from a seated position.

Data Analysis Respiratory heat loss (RHL) was calculated using the standard formula (13). The inspired and expired temperature used in the calculations were measured by the YSI thermistor in the Daniels' valve. The water content values for inspired and expired air were calculated using standard tables. The severity of EIB was calculated using the percent fall index for FEV" described by Godfrey and colleagues (14): (pre-exercise - lowest postexercise value) 070 fall = (pre-exercise value)

x 100

The pre-exercise value was the one that immediately preceded the challenge in question. The degree of protection for each trial was calculated using the percent decrease in pulmonary function to create the index of protection reported by Schoeffel and coworkers (15): standard bout 0J0 decrease - CH-2 0J0 decrease standard bout 0J0 decrease

Index 070

x 100

Paired t tests were used to identify any

TABLE 2 CARDIORESPIRATORY AND METABOLIC FUNCTIONS DURING EXERCISE' Session A Standard Bout HR, bpm

VE, Llmin

t, breaths/min VT, L YO"~ Llmin Yeo"~ Llmin VENO,

CH-1 174 70.9 37 1.9 2.2 2.4 25.9

± ± ± ± ± ± ±

9 13.6 6 0.3 0.5 0.5 3.7

Session B CH-2

178 72.3 40 1.9 2.3 2.4 25.0

± ± ± ± ± ± ±

9 14.1 5 0.3 0.5 0.6 4.0

CH-1 175 75.0 37 2.0 2.6 2.4 22.9

± ± ± ± ± ± ±

10 17.8 6 0.4 0.6t 0.6 2.2t

Session C CH-2

177 72.2 38 2.0 2.2 2.4 26.2

± ± ± ± ± ± ±

10 14.3 8 0.4 0.6 0.5 4.8

CH-1 146 59.3 35 1.7 1.6 1.7 30.0

± ± ± ± ± ± ±

20t 20.2t 11 0.4 0.5t 0.6t 4.8t

CH-2 174 72.6 37 2.0 2.3 2.4 25.4

± ± ± ± ± ± ±

9 17.2 6 0.4 0.5 0.6 4.7

Definition of abbreviations: CH-l = challenge 1; CH-2 = challenge 2; HR = heart rate; VE = minute ventilation; f = respiratory frequency; VT = tidal volume; vo, = oxygen consumption; Veo, = carbon dioxide production. • Values are mean ± SO. t Values were significantly different from the standard test (p < 0.05).

351

ROLE OF EXERCISE AND BRONCHOCONSTRICTION IN INITIATING REFRACTORINESS

rABLE 3 FEV, DATA AND PERCENT PROTECTION INDEX FOR ALL SUBJECTS Session A

Session B CH-2

CH-l

CH-l

Session C CH-2

CH-l

CH-2

Subject

Pre Post

Pre

Post

%PI

Pre

Post

Pre

Post

%PI

Pre

Post

Pre

Post

%PI

CB DM HH NL MF CP BW SS

4.2 4.0 3.0 3.2 4.7 3.2 3.8 4.8

4.2 3.9 2.9 2.8 4.6 3.0 3.9 4.6

4.0 2.8 2.4 2.0 3.4 2.7 2.6 4.4

78 44 56 50 44 60 51 71

4.8 3.8 2.8 3.3 4.7 2.8 3.6 4.8

4.6 3.3 2.8 3.0 4.1 2.7 2.9 4.8

4.8 3.7 3.2 3.2 4.6 2.8 3.4 4.9

4.5 3.0 2.8 2.6 3.8 2.5 1.4 4.4

70 62 69 70 63 57 14 39

4.4 4.4 3.0 3.2 4.8 2.7 3.2 4.9

4.4 4.4 2.7 3.0 4.2 2.4 2.7 4.8

4.5 4.4 3.0 3.2 4.6 2.8 3.5 4.9

4.3 4.0 2.6 2.2 3.9 2.3 1.3 4.5

79 80 57 50 67 28 8 51

3.3 2.0 1.8 1.2 2.5 2.4 1.2 4.0

Definition of abbreviations: CH-1 = challenge 1; CH-2 = challenge 2; %PI = percent protection index.

A significant protection against EIB, as measured by MEF50, was shown in all sessions: 671110 for Session A, 63% for B, and 58% for C. The respective protection for FEV 1 was 56% for Session A, 55% for B, and 51% for C. There was no significant difference in percent protection in terms of either MEF 50 or FEV 1 among the three sessions. Discussion

All 12 of the original subjects met the first selection criterion, having EIB. This response was probably due to the optimal setting of the standard test, which was a 6-min treadmill run at an intensity of 85 to 90% maximal HR, performed in a dry environment (5, 11, 12, 16). Eight of these 12 subjects also showed a sig-

nificant refractory period in Session A and were allowed to complete all three experimental sessions. For the protection provided by the initial exercise challenges to be quantified and compared, all CH-2 bouts must be performed under identical conditions. This was accomplished as there were no significant differences in V0 2 , VE, or RHL among any of these tests; however, although the airway challenge was similar among these tests, the EIB was significantly reduced for all CH-2 conditions. This was consistent for both the FEV 1 and MEF 50 data, suggesting protection from constriction in large and small airways alike. In the present study, similar refractory periods to an identical exercise challenge resulted even though three quite

CJ Challenge 1 ~ Challenge 2

50 40 ~ ~

FEV 1

30

MEF50

Effects of humid air breathing during arm or treadmill exercise on exercise-induced bronchoconstriction and refractoriness.

Although it has been reported that inhibitory prostaglandins may be a causal factor in exercise refractoriness, it is still unclear whether exercise-i...
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